Neutrophil Traction Stresses are Concentrated in the Uropod during Migration

Smith, Lee A.; Aranda‐Espinoza, Helim; Haun, Jered B.; Dembo, Micah; Hammer, Daniel A.

doi:10.1529/biophysj.106.102822

Cited by 108 publications

(140 citation statements)

References 19 publications

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“…This latter observation is consistent with previous reports of T-cell crawling, showing that adhesion and migration properties are mediated by integrin/ ICAM binding and affinity regulation in the front and central body 14 . In contrast, the former observation of non-adherence of the cell rear is surprising relative to existing paradigms on cell motility: for mesenchymatous cells, cell rear is clearly adherent and requires strong actomyosin traction to detach 15 , and for amoeboid cells, actomyosin traction is also reported to be concentrated in uropods 16 . Nevertheless, the non-adherence of lymphocytes uropods is directly relevant for flow-guided migration, as it allows the fast rotation and orientation of uropods with flow in the plane of the substrate, which is similar to a free-rotating wind vane (Supplementary Note 1 and Supplementary Fig.…”

Section: Resultsmentioning

confidence: 63%

“…The physiological benefit of flow orientation is currently unknown for lymphocytes and more generally for neutrophils 16 , endothelial cells 9 or amoebae 23 . The fact that neutrophils crawl downstream 16 and T lymphocytes upstream 4 while migrating on the same adhesive ligand, challenges the idea of a universal flowguided mechanism selected to favour extravasation.…”

Section: Discussionmentioning

confidence: 99%

“…The fact that neutrophils crawl downstream 16 and T lymphocytes upstream 4 while migrating on the same adhesive ligand, challenges the idea of a universal flowguided mechanism selected to favour extravasation. Furthermore, as upstream crawling may not rely on a specific signalling mechanism, one cannot exclude that flow orientation may be a fortuitous consequence of uropod morphology.…”

Section: Discussionmentioning

confidence: 99%

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Lymphocytes can self-steer passively with wind vane uropods

et al. 2014

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A wide variety of cells migrate directionally in response to chemical or mechanical cues, however the mechanisms involved in cue detection and translation into directed movement are debatable. Here we investigate a model of lymphocyte migration on the inner surface of blood vessels. Cells orient their migration against fluid flow, suggesting the existence of an adaptive mechano-tranduction mechanism. We find that flow detection may not require molecular mechano-sensors of shear stress, and detection of flow direction can be achieved by the orientation in the flow of the non-adherent cell rear, the uropod. Uropods act as microscopic wind vanes that can transmit detection of flow direction into cell steering via the on-going machinery of polarity maintenance, without the need for novel internal guidance signalling triggered by flow. Contrary to chemotaxis, which implies active regulation of cue-dependent signalling, upstream flow mechanotaxis of lymphocytes may only rely on a passive self-steering mechanism.

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Section: Resultsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lymphocytes can self-steer passively with wind vane uropods

et al. 2014

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“…However, less is known about how the back of the cell may regulate signaling at the front and modulate cell polarity. There is evidence to support a role for the uropod in regulating cell polarity (Lee et al, 2004), and recent studies suggest that the uropod provides an area where contractile stresses are concentrated (Smith et al, 2007) and may play a more active role in cell motility by regulating integrin clustering through WASP (Zhang et al, 2006). This raises the intriguing possibility that the cell rear may be an active signaling module that regulates cell polarity and provides positive feedback to the front of the cell during directed cell migration.…”

Section: Discussionmentioning

confidence: 99%

Type Iγ PIP Kinase Is a Novel Uropod Component that Regulates Rear Retraction during Neutrophil Chemotaxis

Lokuta

Senetar²,

Bennin

et al. 2007

MBoC

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Cell polarization is necessary for directed migration and leukocyte recruitment to inflamed tissues. Recent progress has been made in defining the molecular mechanisms that regulate chemoattractant-induced cell polarity during chemotaxis, including the contribution of phosphoinositide 3-kinase (PI3K)-dependent phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P 3 ] synthesis at the leading edge. However, less is known about the molecular composition of the cell rear and how the uropod functions during cell motility. Here, we demonstrate that phosphatidylinositol phosphate kinase type I␥ (PIPKI␥661), which generates PtdIns(4,5)P 2 , is enriched in the uropod during chemotaxis of primary neutrophils and differentiated HL-60 cells (dHL-60). Using time-lapse microscopy, we show that enrichment of PIPKI␥661 at the cell rear occurs early upon chemoattractant stimulation and is persistent during chemotaxis. Accordingly, we were able to detect enrichment of PtdIns(4,5)P 2 at the uropod during chemotaxis. Overexpression of kinase-dead PIPKI␥661 compromised uropod formation and rear retraction similar to inhibition of ROCK signaling, suggesting that PtdIns(4,5)P 2 synthesis is important to elicit the backness response during chemotaxis. Together, our findings identify a previously unknown function for PIPKI␥661 as a novel component of the backness signal that regulates rear retraction during chemotaxis.

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“…More importantly, we found that cross-linking of surface expressed CD81 and CD63 with specific mAb significantly enhanced migration of NK cells toward various inflammatory and lymphoid chemokines/cytokines. In contrast, Ab directed against CD9 and CD151 did not affect NK cell motility.Formation of an asymmetric front-rear axis is an essential requirement for efficient directional lymphocyte movement [24,25,29,30]. This polarization segregates two cell compartments with specific properties, composition, and functions: the leading edge at the front and the uropod at the rear.…”

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confidence: 99%

Regulation of NK cell trafficking by CD81

et al. 2009

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NK cells, a heterogeneous sub-population of lymphocytes, are critically involved in the regulation of both innate and adaptive immune responses in humans. Besides their participation in the control of tumors and viral infections, they also regulate inflammatory processes, mediating both beneficial and detrimental effects. To effectively fulfil their role in immune surveillance, proper trafficking of NK cells is essential. However, the mechanisms and factors governing NK cell recruitment are only poorly dissected. Here, we describe the functional role of tetraspanins, a family of evolutionary conserved cellsurface proteins, in modulating migration and transmigration of human NK cells. We demonstrate expression of various tetraspanins on NK cells. Furthermore, we show that stimulation of the NK cell-expressed tetraspanin CD81 induces phosphorylation of ezrin/ radixin/moesin proteins and leads to NK cell polarization thereby facilitating NK cell migration toward various chemokines/cytokines. Finally, we provide evidence for a role of CD81 in promoting adhesion of NK cells to components of the extracellular matrix, a prerequisite for extravasation of lymphocytes in inflamed tissues. Thus, our data suggest that the tetraspanin CD81 is importantly involved in the regulation of NK cell recruitment.Key words: Adhesion . Cell migration . Cell trafficking . Chemokines . NK cells Supporting Information available onlineIntroduction NK cells, a heterogeneous sub-population of lymphocytes, are a central part of the innate immune system. Due to their ability to rapidly attack target cells without prior immunization, NK cells can control infection by viruses, and many studies indicate a role for NK cells in the control of tumor development in mice [1]. Moreover, NK cells are also involved in the regulation of adaptive immune responses via secretion of pro-inflammatory cytokines [2] and modulation of interactions between APC and T cells. In addition, NK cells can act as APC themselves [3].In contrast to their beneficial role in the control of malignancies and invading pathogens, NK cells have been shown to also act as mediators of innate immunopathology (reviewed in [1]). Thus, NK cells do not only participate in the control of tumors and viral infections, but also regulate inflammatory processes and influence subsequent adaptive immune responses, mediating both beneficial and detrimental effects.To fulfil their role in immune surveillance, proper trafficking of NK cells is essential. In general, NK cells are found widely Eur. J. Immunol. 2009. 39: 3447-3458 DOI 10.1002 Innate immunity 3447 distributed in the body. Upon inflammation, NK cells are rapidly recruited into various organs such as the lung, liver, or central nervous system following gradients of chemokines and lysolipids, and can then extravasate into the parenchyma or body cavities, resulting in marked NK cell accumulation within inflamed tissues/organs. This requires that NK cells interact with the vessel wall under flow conditions, arrest, and transmigrate. All th...

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Neutrophil Traction Stresses are Concentrated in the Uropod during Migration

Cited by 108 publications

References 19 publications

Lymphocytes can self-steer passively with wind vane uropods

Lymphocytes can self-steer passively with wind vane uropods

Type Iγ PIP Kinase Is a Novel Uropod Component that Regulates Rear Retraction during Neutrophil Chemotaxis

Regulation of NK cell trafficking by CD81

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